The parkin gene and its phenotype

Mutations of the parkin gene on chromosome 6 cause autosomal recessive, ear ly onset parkinsonism. This is the most frequent form of monogenic parkinso nism so far identified. The associated phenotypical spectrum encompasses ea rly onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with th e earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at a utopsy in brains of patients with parkin mutations. The parkin protein poss esses ubiquitin ligase activity, which is abolished by the pathogenic mutat ions.